We approached the characterization of mutations responsible for inherited neurological or psychiatric disorders by studying the gene organization of specific proteins that might have a role in the pathogenesis of the clinical manifestations. Using the inherited lysosomal storage disorder, Gaucher disease, as a model, we demonstrated that the phenotypic heterogeneity seen within these inherited disorders is a consequence of different mutations, each affecting protein activity and influencing the processing, compartmentalization and/or stability of the protein. Southern analysis and polymerase chain amplification is used to identify mutations in Gaucher disease that frequently occur in both non-neuronopathic and neuronopathic phenotypes. The molecular mechanisms leading to nervous system involvement in these disorders have also been investigated. The results of this research should provide a more rational foundation for the diagnosis and formulation of therapeutic strategies for these inherited disorders. Similar approaches are being used to investigate the involvement of candidate genes in bipolar illness and other psychiatric disorders. Recombinant DNA techniques have been used to identify genes that may be involved in neuropsychiatric disorders. Genes specific for neurotransmitter biosynthesis (for example, human tyrosine hydroxylase and tryptophan hydroxylase) and receptors (for example, human GABA receptor) have been isolated. Linkage analysis and candidate gene identification continues in Amish bipolar patients. Recombinant DNA expression systems have been used to produce large amounts of brain proteins for structural and biochemical studies.